PRIMARY SCLEROSING CHOLANGITIS
Department of Medicine
Definition
• Primary Sclerosing Cholangitis = a chronic progressive disorder of unknown etiology that is characterized by inflammation, fibrosis, and stricturing of medium and large ducts in the intrahepatic and/or extrahepatic biliary tree
Epidemiology
• Incidence rate 1 case per 100,000 person-years• 70% (men)• 90% with PSC also have Ulcerative Colitis• 10% with Ulcerative Colitis have PSC
Risk Factors
• Male gender• Inflammatory bowel disease (ulcerative colitis > crohn’s)• First-degree relatives of patients with PSC
Pathogenesis
• Unknown etiology however likely that immunologically-mediated bile duct injury is a major mechanism leading to PSC
Symptoms
• Fatigue• Pruritus• Jaundice• Episodic cholangitis symptoms (biliary obstruction)
– Fevers– Chills– Night sweats– right upper quadrant pain
• 50% asymptomatic – diagnosed during investiation for abnormal LFT’s
Signs
• Excoriations• Jaundice• Hepatomegaly• Splenomegaly
• 50% Normal Physical Exam
Differential Diagnosis
• Alcoholic liver disease• Nonalcoholic fatty liver disease• Viral Hepatitis
– Chronic hepatitis C– Chronic hepatitis B
• Autoimmune hepatitis• Primary sclerosing cholangitis• Medications
– Methotrexate– Amiodarone– isoniazid
• Hereditary– Hereditary hemochromatosis– Wilson disease– Alpha-1-antitrypsin deficiency
investigations
Abnormal LFT’s “cholestatic pattern”• Elevated alkaline phosphatase• Elevated 5'-nucleotidase• Elevated gammaglutamyl transpeptidase• Normal or Slightly elevated ALT (< 300 IU)• Normal or Slightly elevated AST (< 300 IU)• Elevated bilirubin
• Liver Ultrasound– abnormal bile ducts
• Cholangiogram– multifocal stricturing and dilation of intrahepatic and/or extrahepatic bile ducts
• magnetic resonance cholangiopancreatography (MRCP) (1st line)• endoscopic retrograde cholangiopancreatography (ERCP) (2nd line)• percutaneous transhepatic cholangiography (PTC) (3rd line)
Investigation
Investigations
• liver biopsy (Not Indicated For Diagnosis)– staging the disease– determining prognosis
PSC Histology
Stage Zero Normal Liver
Stage one Enlargement, edema, and scarring of the portal triads
Stage two Expansion of portal triads with fibrosis extending into the surrounding parenchyma
Stage three Bridging fibrosis
Stage four Cirrhosis
Investigations
Screening• Annual Abdominal Ultrasound
– gallbladder (Gallbladder carcinoma)– liver (Cholangiocarcinoma)
• carcinoembryonic antigen (CEA)• CA 19-9 • Annual Colonscopy (Colorectal carcinoma)• 2 yearly DEXA bone density Scan
If cirrhosis• Annual α-Feto protein (Hepatocellular Carcinoma)• Annual Liver Ultrasound (Hepatocellular carcinoma)
Treatment
Pruritis / Jaundice• No proven role for medical therapy• Endoscopic treatment of dominant strictures dilate and/or stent
• Liver transplantation
Complications
• Fat soluble vitamin deficiencies (A, D, E, and K)• Metabolic bone disease• Cholangitis and cholelithiasis• Cholangiocarcinoma• Gallbladder cancer• Hepatocellular carcinoma (in patients with cirrhosis)• Colon cancer (in patients with concomitant ulcerative colitis)
Prognosis
• Median survival without liver transplantation after diagnosis is 10 to 12 years
References
• Tung, BY, Brentnall, T, Kowdley, KV, et al. Diagnosis and prevalence of ulcerative colitis in patients with sclerosing cholangitis. Hepatology. 1996; 24:169
• UpToDate• American Association for the Study of Liver diseases Guidelines 2010
Sample MCQ
A 60 year old man with a history of 15 year ulcerative colitis, presents to his family doctor with 3 month progressive history of fatigue, pruritus, jaundice. On examination he has scratch marks on his arms and abdomen, scleral icterus, hepatomegaly and splenomegaly. His Liver function tests are abnormal with elevated Bilirubin, elevated alkaline phosphatase and yGT but normal ALT / AST. What is the most likely investigation to identify the underlying condition?
a)Anti-mitochondrial antibody
b)Hepatitis B Serology
c)HIV Serology
d)Liver Biopsy
e)MRCP
Answer = e
A 60 year old man with a history of 15 year ulcerative colitis, presents to his family doctor with 3 month progressive history of fatigue, pruritus, jaundice. On examination he has scratch marks on his arms and abdomen, scleral icterus, hepatomegaly and splenomegaly. What treatment is most appropriate given the scenario above
a)Cholestyramine
b)Liver transplantation
c)Naltrexone
d)Rifampicin
e)Ursodeoxycholic acid
Answer = b
Sample MCQ
A 60 year old man with a history of 15 year ulcerative colitis, presents to his family doctor with 3 month progressive history of fatigue, pruritus, jaundice. On examination he has scratch marks on his arms and abdomen, scleral icterus, hepatomegaly and splenomegaly. Which is the most appropriate imaging to diagnose Primary Sclerosing Cholangitis?
a)ERCP
b)MRCP
c)PTC
d)US Abdomen
e)CT Abdomen
Answer = b
Sample MeQ
A 60 year old man with a history of 15 year ulcerative colitis, presents to his family doctor with 3 month progressive history of fatigue, pruritus, jaundice. On examination he has scratch marks on his arms and abdomen, scleral icterus, hepatomegaly and splenomegaly.
a)Name 5 differential Diagnosis of primary sclerosing cholangitis ( 5 marks)
See slide 8
b)List 4 complications of primary sclerosing cholangitis ( 4 marks)
See slide 14
c)Name 2 treatment options for Primary sclerosing cholangitis ( 4 marks)
Endoscopic treatment of dominant strictures dilate and/or stent
Liver transplantation
d)Name 1 autoimmune test that distinguishes primary sclerosing cholangitis from primary biliary cirrhosis ( 3 marks)
Anti-mitochondrial antibody